{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chowdhury S"],"funding":["Council of Scientific and Industrial Research","Council of Scientific and Industrial Research (CSIR)"],"pagination":["405"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405666"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Derangements in protein homeostasis and associated proteotoxicity mark acute, chronic, and drug-induced hepatocellular injury. Metabolic dysfunction-associated proteasomal inhibition and the use of proteasome inhibitors often underlie such pathological hepatic proteotoxicity. In this study, we sought to identify a candidate deubiquitinating enzyme (DUB) responsible for reversing the proteotoxic damage. To this end, we performed a siRNA screening wherein 96 DUBs were individually knocked down in HepG2 cells under proteasomal inhibitor-induced stress for dual readouts, apoptosis, and cell viability. Among the putative hits, we chose JOSD1, a member of the Machado-Josephin family of DUBs that reciprocally increased cell viability and decreased cell death under proteotoxicity. JOSD1-mediated m"],"journal":["Cell death discovery"],"pubmed_title":["Deubiquitinase JOSD1 tempers hepatic proteotoxicity."],"pmcid":["PMC11405666"],"funding_grant_id":["MLP138"],"pubmed_authors":["Das D","Chowdhury S","Chakrabarti P","Sen A"],"additional_accession":[]},"is_claimable":false,"name":"Deubiquitinase JOSD1 tempers hepatic proteotoxicity.","description":"Derangements in protein homeostasis and associated proteotoxicity mark acute, chronic, and drug-induced hepatocellular injury. Metabolic dysfunction-associated proteasomal inhibition and the use of proteasome inhibitors often underlie such pathological hepatic proteotoxicity. In this study, we sought to identify a candidate deubiquitinating enzyme (DUB) responsible for reversing the proteotoxic damage. To this end, we performed a siRNA screening wherein 96 DUBs were individually knocked down in HepG2 cells under proteasomal inhibitor-induced stress for dual readouts, apoptosis, and cell viability. Among the putative hits, we chose JOSD1, a member of the Machado-Josephin family of DUBs that reciprocally increased cell viability and decreased cell death under proteotoxicity. JOSD1-mediated m","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2025-04-05T18:45:16.888Z","creation":"2025-04-05T18:45:16.888Z"},"accession":"S-EPMC11405666","cross_references":{"pubmed":["39284830"],"doi":["10.1038/s41420-024-02177-y"]}}